Several new monoclonal antibodies have been raised to leukemia-associated antigens. Some of these appear to be detecting differentiation antigens and are important for the phenotyping of leukemia. Among these are: (1)\CT2, which reacts with all E rosette-positive cells; (2)\CB2, which reacts with surface membrane immunoglobulin-positive cells; (3)\CG1, which reacts with granulocytes and CML; and (4)\CBL1, which reacts with blast cells. With these and other monoclonal antibodies, it is now possible to phenotype leukemia by using a 2-hr microcytotoxicity test. We also produced a monoclonal antibody against common ALL that cross reacts with platelets. It detects a cell membrane antigen of 26 kilodaltons. New monoclonal antibodies to T ALL were produced that do not react to normal cells, including bone marrow stem cells. One of these was raised to nonprimate cells transformed by oncogenic virus and may be related to oncogene products. Two of the antibodies, CBL1 and CT2, were previously tested in in vitro and animal models and have now been extended to clinical trials. CBL1 has been shown to reverse dramatically kidney transplant rejection in 19 patients. This antibody appears to be specifically destroying the activated blast cells that are rejecting the graft, and as such, it appears to be a safer, more effective immunosuppressive agent. CT2 is highly specific and cytotoxic to mature T cells and has been very successfully used to reduce dramatically the incidence of graft-versus-host disease (GVHD) in bone marrow transplant (BMT) patients. CT2 and complement treatment were shown to reduce the levels of mature T cells from allogeneic bone marrow prior to transplantation to less than 0.5%. The incidence of GVHD, which is currently a major problem in BMT, was virtually eliminated in matched transplants (18 patients in two different centers) and reduced to four acute cases in 23 mismatch cases. These results provide new hope for patients who do not have matched donors. (AG)